Recovery from surgery may be complicated by postoperative cognitive dysfunction (POCD), especially in high-risk patients [1]. Postoperative complications, for example infection, have been associated with higher incidence of POCD although the mechanisms governing the interaction in the pathogenesis of POCD are not known [2]. Recently, neuroinflammation has been correlated with cognitive decline [3,4]. In this study we sought to understand the effect of postoperative lipopolysaccharide (LPS) on inflammation and POCD-associated behavior after orthopedic surgery.